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Background: Brain and cognitive development during the first 1000 days from conception are affected by multiple biomedical and socioenvironmental determinants including nutrition, health, nurturing, and stimulation. An improved understanding of the long-term influence of these factors is needed to prioritise public health investments to optimise human development., Methods: We did a follow-up study of the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind, cluster-randomised trial of maternal supplementation with multiple micronutrients (MMN) or iron and folic acid (IFA) in Indonesia. Of 27 356 live infants from birth to 3 months of age in 2001-04, we re-enrolled 19 274 (70%) children at age 9-12 years, and randomly selected 2879 from the 18 230 who were attending school at a known location. Of these, 574 children were oversampled from mothers who were anaemic or malnourished at SUMMIT enrolment. We assessed the effects of MMN and associations of biomedical (ie, maternal and child anthropometry and haemoglobin and preterm birth) and socioenvironmental determinants (ie, parental education, socioeconomic status, home environment, and maternal depression) on general intellectual ability, declarative memory, procedural memory, executive function, academic achievement, fine motor dexterity, and socioemotional health. The SUMMIT trial was registered, number ISRCTN34151616., Findings: Children of mothers given MMN had a mean score of 0·11 SD (95% CI 0·01-0·20, p=0·0319) higher in procedural memory than those given IFA, equivalent to the increase in scores with half a year of schooling. Children of anaemic mothers in the MMN group scored 0·18 SD (0·06-0·31, p=0·0047) higher in general intellectual ability, similar to the increase with 1 year of schooling. Overall, 18 of 21 tests showed a positive coefficient of MMN versus IFA (p=0·0431) with effect sizes from 0·00-0·18 SD. In multiple regression models, socioenvironmental determinants had coefficients of 0·00-0·43 SD and 22 of 35 tests were significant at the 95% CI level, whereas biomedical coefficients were 0·00-0·10 SD and eight of 56 tests were significant, indicating larger and more consistent impact of socioenvironmental factors (p<0·0001)., Interpretation: Maternal MMN had long-term benefits for child cognitive development at 9-12 years of age, thereby supporting its role in early childhood development, and policy change toward MMN. The stronger association of socioenvironmental determinants with improved cognition suggests present reproductive, maternal, neonatal, and child health programmes focused on biomedical determinants might not sufficiently enhance child cognition, and that programmes addressing socioenvironmental determinants are essential to achieve thriving populations., Funding: Grand Challenges Canada Saving Brains Program., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: We investigated the relative benefit of maternal multiple micronutrient (MMN) supplementation during pregnancy and until 3 months postpartum compared with iron/folic acid supplementation on child development at preschool age (42 months)., Methods: We assessed 487 children of mothers who participated in the Supplementation with Multiple Micronutrients Intervention Trial, a cluster-randomized trial in Indonesia, on tests adapted and validated in the local context measuring motor, language, visual attention/spatial, executive, and socioemotional abilities. Analysis was according to intention to treat., Results: In children of undernourished mothers (mid-upper arm circumference <23.5 cm), a significant benefit of MMNs was observed on motor ability (B = 0.39 [95% confidence interval (CI): 0.08-0.70]; P = .015) and visual attention/spatial ability (B = 0.37 [95% CI: 0.11-0.62]; P = .004). In children of anemic mothers (hemoglobin concentration <110 g/L), a significant benefit of MMNs on visual attention/spatial ability (B = 0.24 [95% CI: 0.02-0.46]; P = .030) was also observed. No robust effects of maternal MMN supplementation were found in any developmental domain over all children., Conclusions: When pregnant women are undernourished or anemic, provision of MMN supplements can improve the motor and cognitive abilities of their children up to 3.5 years later, particularly for both motor function and visual attention/spatial ability. Maternal MMN but not iron/folic acid supplementation protected children from the detrimental effects of maternal undernutrition on child motor and cognitive development.

Maternal caregiving capacity, which is affected in part by cognition and mood, is crucial for the health of mothers and infants. Few interventions aim to improve maternal and infant health through improving such capacity. Multiple micronutrient (MMN) supplementation may improve maternal cognition and mood, since micronutrients are essential for brain function. We assessed mothers who participated in the Supplementation with Multiple Micronutrients Intervention Trial (SUMMIT), a double-blind cluster-randomized trial in Indonesia comparing MMN supplementation to iron and folic acid (IFA) during pregnancy and until three months postpartum. We adapted a set of well-studied tests of cognition, motor dexterity, and mood to the local context and administered them to a random sample of 640 SUMMIT participants after an average of 25 weeks (SD = 9) of supplementation. Analysis was by intention to treat. Controlling for maternal age, education, and socio-economic status, MMN resulted in a benefit of 0.12 SD on overall cognition, compared to IFA (95%CI 0.03-0.22, p = .010), and a benefit of 0.18 SD on reading efficiency (95%CI 0.02-0.35, p = .031). Both effects were found particularly in anemic (hemoglobin<110 g/L; overall cognition: B = 0.20, 0.00-0.41, p = .055; reading: B = 0.40, 0.02-0.77, p = .039) and undernourished (mid-upper arm circumference<23.5 cm; overall cognition: B = 0.33, 0.07-0.59, p = .020; reading: B = 0.65, 0.19-1.12, p = .007) mothers. The benefit of MMN on overall cognition was equivalent to the benefit of one year of education for all mothers, to two years of education for anemic mothers, and to three years of education for undernourished mothers. No effects were found on maternal motor dexterity or mood. This is the first study demonstrating an improvement in maternal cognition with MMN supplementation. This improvement may increase the quality of care mothers provide for their infants, potentially partly mediating effects of maternal MMN supplementation on infant health and survival. The study is registered as an International Standard Randomized Controlled Trial, number ISRCTN34151616. http://www.controlled-trials.com/ISRCTN34151616.

Background: Evaluating the impact of nutrition interventions on developmental outcomes in developing countries can be challenging since most assessment tests have been produced in and for developed country settings. Such tests may not be valid measures of children's abilities when used in a new context., Aims: We present several principles for the selection, adaptation, and evaluation of tests assessing the developmental outcomes of nutrition interventions in developing countries where standard assessment tests do not exist. We then report the application of these principles for a nutrition trial on the Indonesian island of Lombok., Sample: Three hundred children age 22-55 months in Lombok participated in a series of pilot tests for the purpose of test adaptation and evaluation. Four hundred and eighty-seven 42-month-old children in Lombok were tested on the finalized test battery., Methods: The developmental assessment tests were adapted to the local context and evaluated for a number of psychometric properties, including convergent and discriminant validity, which were measured based on multiple regression models with maternal education, depression, and age predicting each test score., Results: The adapted tests demonstrated satisfactory psychometric properties and the expected pattern of relationships with the three maternal variables. Maternal education significantly predicted all scores but one, maternal depression predicted socio-emotional competence, socio-emotional problems, and vocabulary, while maternal age predicted socio-emotional competence only., Conclusion: Following the methodological principles we present resulted in tests that were appropriate for children in Lombok and informative for evaluating the developmental outcomes of nutritional supplementation in the research context. Following this approach in future studies will help to determine which interventions most effectively improve child development in developing countries.